Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control* ; Animals ; Hypericum/chemistry* ; Phloroglucinol/administration & dosage* ; Mice ; Humans ; Male ; Liver/blood supply* ; Apoptosis/drug effects* ; Molecular Structure ; Protective Agents/pharmacology* ; Hepatocytes/drug effects* ; Mice, Inbred C57BL ; Liver Diseases/drug therapy*

Liver diseases have become a major challenge threating the global health, posing a heavy burden on both social and personal well-being. In recent years, the development of the gut-liver axis theory has provided new research perspectives and intervention strategies for the prevention and treatment of liver diseases. Natural products, recognized as biological molecules with diverse sources, rich activities, and minimal side effects, demonstrate great potential in regulating intestinal flora and improving liver health. Studies have shown that natural products such as saponins, polyphenols, polysaccharides, and alkaloids can regulate the composition and metabolites of intestinal flora, thereby intervening in liver diseases. In this paper, we systematically review the role of natural products in the regulation of the intestinal flora-gut-liver axis and summarize recent research progress in the prevention and treatment of liver diseases. Furthermore, we outline the challenges and limitations currently facing the study in this field. Finally, this paper makes an outlook on the clinical application of natural products in treating liver diseases and discusses future research directions, aiming to give new insights into the mechanisms by which natural products regulate the intestinal flora-gut-liver axis and the applications of these products in the prevention and treatment of liver diseases.
Humans ; Gastrointestinal Microbiome/drug effects* ; Liver Diseases/prevention & control* ; Biological Products/pharmacology* ; Polyphenols/pharmacology* ; Saponins/pharmacology* ; Intestines/microbiology* ; Alkaloids/pharmacology* ; Polysaccharides/pharmacology* ; Liver

Ornithine transcarbamylase deficiency(OTCD)is a most common ornithine cycle (urea cycle) disorder. It is a X-link inherited disorder caused by
Humans ; Hyperammonemia/etiology* ; Liver Transplantation ; Nervous System Diseases/prevention & control* ; Ornithine Carbamoyltransferase Deficiency Disease/therapy*

Antrodia camphorata, a well-known and highly valued edible medicinal mushroom with intriguing activities like liver protection, has been traditionally used for the treatment of alcoholic liver disease. A. camphorata shows highly medicinal and commercial values with the demand far exceeds the available supply. Thus, the petri-dish cultured A. camphorata (PDCA) is expected to develope as a substitute. In this paper, nineteen triterpenes were isolated from PDCA, and thirteen of them were the unique anthroic acids in A. camphorata, including the main content antcin K, which suggested that PDCA produced a large array of the same anthroic acids as the wild one. Furthermore, no obvious acute toxicity was found suggesting the edible safety of PDCA. In mice alcohol-induced liver injury model, triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) had been reduced by the PDCA powder as well as the main content antcin K, which indicated that the PDCA could protect alcoholic liver injury in mice model and antcin K could be the effective component responsible for the hepatoprotective activities of PDCA against alcoholic liver diseases.
Alanine Transaminase ; blood ; Aldehyde Dehydrogenase ; blood ; Animals ; Antrodia ; chemistry ; Aspartate Aminotransferases ; blood ; Biological Products ; chemistry ; pharmacology ; therapeutic use ; Chemical and Drug Induced Liver Injury ; etiology ; prevention & control ; Cholestenes ; chemistry ; pharmacology ; therapeutic use ; Cholesterol, VLDL ; blood ; Disease Models, Animal ; Ethanol ; toxicity ; Female ; Fruiting Bodies, Fungal ; chemistry ; Liver ; drug effects ; metabolism ; pathology ; Liver Diseases, Alcoholic ; prevention & control ; Male ; Malondialdehyde ; blood ; Mice ; Molecular Structure ; Triglycerides ; blood ; Triterpenes ; chemistry ; pharmacology ; therapeutic use

Cholangiocarcinoma (CCA) is an aggressive cancer arising from epithelial cells of the bile duct. Most patients with CCA have an unresectable tumor at the time of diagnosis. In Western countries, the risk of CCA increases in patients with primary sclerosing cholangitis, whereas liver fluke infection appears to be the major risk factor for CCA in Asian countries. A diagnosis of liver fluke infection often relies on stool samples, including microscopic examination, polymerase chain reaction-based assays, and fluke antigen detection. Tests of serum, saliva and urine samples are also potentially diagnostic. The presence of liver fluke along with exogenous carcinogens magnifies the risk of CCA in people living in endemic areas. The “liver fluke-cholangiocarcinoma” carcinogenesis pathways consist of mechanical damage to the bile duct epithelium, immunopathologic and cellular reactions to the liver fluke's antigens and excretory/secretory products, liver fluke-induced changes in the biliary tract microbiome and the effects of repeated treatment for liver fluke. A vaccine and novel biomarkers are needed for the primary and secondary prevention of CCA in endemic areas. Importantly, climate change exerts an effect on vector-borne parasitic diseases, and awareness of liver fluke should be enhanced in potentially migrated habitat areas.
Asian Continental Ancestry Group ; Bile Ducts ; Biliary Tract Neoplasms* ; Biliary Tract* ; Biomarkers ; Carcinogenesis ; Carcinogens ; Cholangiocarcinoma ; Cholangitis, Sclerosing ; Climate Change ; Clonorchiasis ; Diagnosis ; Ecosystem ; Epithelial Cells ; Epithelium ; Fasciola hepatica ; Humans ; Liver* ; Microbiota ; Opisthorchiasis ; Parasitic Diseases ; Risk Factors ; Saliva ; Secondary Prevention ; Trematoda

Hepatitis B virus (HBV) infection is the most common cause of chronic liver diseases in Korea. After the introduction of the universal HBV vaccination program, the prevalence of hepatitis B surface antigen was markedly reduced, and Korea is now classified as an area of intermediate endemicity for HBV. However, there are still hurdles for elimination of hepatitis B, such as immunoprophylaxis failure against vertical transmission, occurrence of acute hepatitis B among peoples who did not have vaccination at younger age, and rapid increase of immigrant populations from HBV endemic areas. To achieve the World Health Organization goal of viral hepatitis elimination by 2030 in Korea, we suggest comprehensive policies for more effective control of hepatitis B as following: i) insurance coverage for antiviral prophylaxis in mothers with high viremia, ii) screening for hepatitis B seromarkers and catch-up HBV vaccinations of susceptible persons with hepatitis B, iii) establishment of an independent ‘viral hepatitis sector’ in Centers for Disease Control & Prevention to organize and execute comprehensive strategy for management of viral hepatitis, iv) encourage of management of HBV infection in immigrant populations, v) national campaign to promote awareness of hepatitis B.
Centers for Disease Control and Prevention (U.S.) ; Emigrants and Immigrants ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B* ; Hepatitis* ; Humans ; Insurance Coverage ; Korea* ; Liver Diseases ; Mass Screening ; Mothers ; Prevalence ; Vaccination ; Viremia ; World Health Organization

Viral hepatitis is one of major global health challenges with increasing disease burden worldwide. Hepatitis B virus and hepatitis C virus infections are major causes of chronic liver diseases. They can lead to cirrhosis, hepatocellular carcinoma, and death in significant portion of affected people. Transmission of hepatitis B virus can be blocked by vaccination. Progression of hepatitis B virus-related liver diseases can be prevented by long-term viral suppression with effective drugs. Although vaccine for hepatitis C virus is currently unavailable, hepatitis C virus infection can be eradicated by oral direct antiviral agents. To eliminate viral hepatitis, World Health Organization (WHO) has urged countries to develop national goals and targets through reducing 90% of new infections and providing universal access to key treatment services up to 80%. This can lead to 65% reduction of viral hepatitis-related mortality. Here, we discuss some key features of viral hepatitis, strategies to control viral hepatitis suggested by WHO, and current status and strategies for viral hepatitis control in South Korea. To achieve the goal of viral hepatitis elimination by 2030 in South Korea, an independent 'viral hepatitis sector' in Centers for Disease Control & Prevention (CDC) needs to be established to organize and execute comprehensive strategy for the management of viral hepatitis in South Korea.
Antiviral Agents ; Carcinoma, Hepatocellular ; Centers for Disease Control and Prevention (U.S.) ; Fibrosis ; Global Health ; Hepacivirus ; Hepatitis A ; Hepatitis B ; Hepatitis B virus ; Hepatitis C ; Hepatitis* ; Korea* ; Liver Diseases ; Mortality ; Vaccination ; World Health Organization

Fascioliasis is a foodborne zoonotic parasitic disease. We report 4 cases occurring in the same family, in whom diagnosis of acute fascioliasis was established after series of tests. One case was hospitalized with fever, eosinophilia, and hepatic lesions. MRI showed hypodense changes in both liver lobes. The remaining 3 cases presented with the symptom of stomachache only. Stool analysis was positive for Fasciola eggs in 2 adult patients. The immunological test and molecular identification of eggs were confirmed at the National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China. The results of serological detection were positive in all the 4 patients. DNA sequencing of PCR products of the eggs demonstrated 100% homology with ITS and cox1 of Fasciola hepatica. The conditions of the patients were not improved by broad-spectrum anti-parasitic drugs until administration of triclabendazole.
Adult ; Asian Continental Ancestry Group ; Centers for Disease Control and Prevention (U.S.) ; China* ; Diagnosis ; Eggs ; Eosinophilia ; Fasciola ; Fasciola hepatica ; Fascioliasis* ; Fever ; Humans* ; Immunologic Tests ; Liver ; Magnetic Resonance Imaging ; Ovum ; Parasitic Diseases ; Polymerase Chain Reaction ; Sequence Analysis, DNA

OBJECTIVE: To investigate the effect of limb remote ischemic preconditioning (RIPC) on hepatic ischemia/reperfusion (IR) injury and the underlying mechanisms.
 METHODS: Rats were subjected to partial hepatic IR (60 min ischemia followed by 24 hours reperfusion) with or without RIPC, which was achieved by 3 cycles of 10 min-occlusion and 10 min-
reperfusion at the bilateral femoral arteries interval 30 min before ischemia. Some rats were treated with a new PPAR-γ inhibitor, T0070907, before RIPC.
 RESULTS: At the end of reperfusion, liver injury was significantly increased (increases in Suzike's injury score, AST and ALT release), concomitant with elevated oxidative stress (increases in MDA formation, MPO activity, as well as the decrease in SOD activity) and inflammation (increases in TNF-α and IL-6 levels, decrease in IL-10 content). RIPC improved liver function and reduced histologic damage, accompanied by the increased PPAR-γ activation and autophagosome formation as well as the reduced autophagosome clearance. The beneficial effects of RIPC were markedly attenuated by T0070907, an inhibitor of PPAR-γ.
 CONCLUSION RIPC exerts the protective effects on liver by activation of autophagy via PPAR-γ.
Animals ; Autophagy ; drug effects ; genetics ; physiology ; Extremities ; Interleukin-10 ; metabolism ; Interleukin-6 ; metabolism ; Ischemia ; Ischemic Preconditioning ; methods ; Liver ; injuries ; Liver Diseases ; prevention & control ; Oxidative Stress ; drug effects ; PPAR gamma ; antagonists & inhibitors ; Rats ; Reperfusion Injury ; prevention & control ; Tumor Necrosis Factor-alpha ; metabolism

To study the protective effect and the mechanism of asiatic acid (AA) from Potentilla chinensis on alcohol hepatic injury in rats. Male Wistar rats were randomly divided into six groups: the normal control group, the AA control group (8 mg · kg(-1) AA), the model group (5.0-9.0 g · kg(-1) alcohol) and high, medium and low-dose AA-treated groups (alcohol + 8, 4, 2 mg · kg(-1) AA). Each group was orally administered with the corresponding drugs once a day for 24 weeks. Approximately 1. 5 hours after the final administration, all rats were killed, and their blood samples and hepatic tissues were collected. The AST and ALT in rat serum and the contents of MPO, TNF-α, IL-1β, SOD, GSH-Px, GSH-Rd and MDA in hepatic tissues were detected. The expressions of NF-κB, TLR4, CD14, MyD88, TRIF and protein expression in hepatic tissues were measured by western blot. The pathological changes in liver tissues were observed by histological examination. The results showed that compared with the model group, the AA-treated groups showed significant decreases in serum ALT, AST and MDA and increases in the activities of SOD, GSH-Px, GSH-Rd and MPO. Moreover, AA markedly inhibited the expressions of TNF-α, IL-1β, TLR4, CD14, MyD88 and NF-κB. The histological examination showed alleviated hepatic issue ijury to varying degrees. In short, asiatic acid (AA) from P. chinensis could protect alcohol-induced hepatic injury in rats. Its mechanism may be related to the inhibition of NF-κB inactivation and the reduction of inflammatory response.
Animals ; Liver ; drug effects ; pathology ; Liver Diseases, Alcoholic ; prevention & control ; Male ; NF-kappa B ; physiology ; Pentacyclic Triterpenes ; pharmacology ; Potentilla ; chemistry ; Protective Agents ; pharmacology ; Rats ; Rats, Wistar ; Toll-Like Receptor 4 ; antagonists & inhibitors